1. Field of the Invention
The present invention relates to a method of preparing a very slightly soluble drug with solid dosage form. More particularly, the present invention relates to a method of preparing a very slightly soluble drug such as improved β-Carboline compound or Triazole.
2. Description of the Prior Art
Since β-Carboline or Triazole compounds are water-insoluble, certain methods have been developed to increase the dissolution rate. PCT Application WO 96/38131 and U.S. Pat. No. 5,985,326) disclose co-precipitation technology. Said technology prepares a drug by forming co-precipitates of a β-Carboline compound and a polymeric material such as hydroxypropyl methyl cellulose phthalate, wherein the co-precipitates are subsequently milled and mixed with the excipient, and then compressed into tablets for oral administration. However, the difficulties arose in generating precisely reproducible lots of coprecipitate product, which makes use of coprecipitates less than ideal in pharmaceutical formulations. Additionally, clinical studies involving administration of coprecipitate tablets preliminarily revealed that maximum blood concentration of the β-carboline compound is achieved in 3 to 4 hours, with the average time for onset of therapeutic effect not yet precisely determined. In the treatment of sexual dysfunction, such as male erectile dysfunction or female sexual arousal disorder, however, a more rapid achievement of maximum blood concentration, along with a greater prospect for rapid onset of therapeutic effect, frequently is sought by individuals desiring more immediate and/or less prolonged effects. Accordingly, a need in the art continues to exist for orally administrable β-carboline compounds and 5-carboline-containing pharmaceutical compositions having an ability to provide a therapeutic effect within a desirable, or at least acceptable, time frame.
Taiwan Patent No. 1235658 discloses a particulate preparations technology of a free drug form and provides particulate preparations of a free drug form of a β-Carboline compound having specific and defined particle size characteristics. U.S. Pat. No. 8,288,394 also discloses a micronized Voriconazole compound having specific and defined particle size characteristics. When 90% of the Voriconazole compound medicament have a particle size less than 150 μm, especially a specific surface area from 0.5 m2/g to 2 m2/g and a Sauter dia meter from 4 μm to 20 μm, this may effectively overcome the insoluble problem of many medicaments. Although the defined particle size may result in an evenly blended stable pharmaceutical composition with increased dissolution rate, it is extremely difficult to find a source of raw materials having specific and defined particle size characteristics, and the quality control thereof also becomes difficult. Consequently, stock preparation and manufacturing may require a lot of time and cost, thus restricting the scope of this technology in practical applications. Therefore, there remains a need for an improved method of preparing the pharmaceutical composition of β-Carboline or Voriconazole compounds while simultaneously increasing the dissolution rate and the bioavailability in the human body.